Controlled treatment studies of patients with obsessive-compulsive disorder (OCD) revealed that the serotonin 5-HT1A receptor partial agonist, buspirone, was as effective as the most well-established therapeutic agent in OCD, clomipramine. However, the addition of buspirone to clomipramine in a group of OCD patients in partial remission yielded no further improvement, suggesting that other ways to modulate brain serotonergic subsystems are needed, and/or other psychobiologic factors need to be considered in attempts to gain additional therapeutic benefit. Some additional initiatives in this direction utilizing lithium and triiodothyronine together with clomipramine led to minimal further benefit, although such cotreatment has been reported to be of value in depressed patients. Additional evidence regarding the importance of serotonin in OCD came from a study demonstrating that pretreatment with the serotonin antagonist, metergoline, blocked the brief exacerbation of OCD symptoms produced by the 5-HT1C serotonin agonist, m-chlorophenylpiperazine.